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Curr Drug Targets. 2017;18(14):1664-1675. doi: 10.2174/1389450118666170104153512.

Pro-Inflammatory Cytokines: New Potential Therapeutic Targets for Obesity-Related Bone Disorders.

Wang T1,2, He C2, Yu X2.

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Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041. China.
Collaborative Innivation Centre of Biotherapy and Cancer Centre, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu. China.



Obesity was traditionally considered as a positive regulator on the strength of bone. With the in-depth study, obesity is considered as a major risk factor for osteoporosis. Some proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) are the factors that fat uses to negatively regulate bone metabolism.


This review was aimed to summarize and critically discuss the convincing evidence for the therapeutic effectiveness of pro-inflammatory cytokines for the treatment of obesity-related bone disorders.


Obese people and animals show a higher level of serum TNF-α and IL-6, which are produced by macrophages derived from adipose tissue. These pro-inflammatory cytokines regulate the proliferation and apoptosis of adipocyte, promote lipolysis, inhibit lipid synthesis and decrease blood lipids through autocrine and paracrine way. On the other hand, TNF-α and IL-6 regulate bone metabolism through the endocrine way. Several reports suggest that TNF-α is a negative regulator of osteoblast at some stages of differentiation and positively regulates osteoclast proliferation and differentiation. In contrast, IL-6 influences osteoblasts and osteoclasts through complex mechanisms, which reflect dual effects. In addition, TNF-α and IL-6 may regulate bone metabolism indirectly by regulating adiponectin and leptin released from adipocytes.


In this review, we first summarize the role of TNF-α and IL-6 in lipid and bone metabolisms. We further discuss how TNF-α and IL-6 regulate the communication between fat and bone, and their pathological roles in obesity-related bone disorders. Lastly, we discuss the possibility of using pro-inflammatory signaling pathway as a therapeutic target to develop drug for obesity-related bone disorders.


IL-6; TNF-α; bone metabolism; lipid metabolism; obesity; osteoporosis

[Indexed for MEDLINE]

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